Synthesis and in vitro evaluation of 2-[¹¹C]methoxyestradiol-3, 17β-O,O-bissulfamate for in vivo studies of angiogenesis

In the present study, 2-methoxyestradiol-3,17β-O,O-bissulfamate (1), a known angiogenesis inhibitor, was prepared in a radiolabeled form by ¹¹C-methylation of 2-hydroxyestradiol-3,17β-O,O-bis(N-trityl) sulfamate (6) followed by detritylation. Synthesis of precursor 6 required a rather long step because of the presence of two sulfamoyl groups. The decay-corrected radiochemical yield of [¹¹C]1 was 19 ± 2% based on [¹¹C]CH₃I, and the specific activity was 34-39 GBq/μmol. Although 1 is known to significantly inhibit the proliferation of human umbilical vascular endothelial cells (HUVECs), its radiolabeled form, [¹¹C]1 was not avidly taken up by HUVECs, and the uptake increased slightly in a time-dependent manner (156% at 60 min relative to a value of 100% at 5 min). These results suggest that further studies are warranted to determine the molecular target for [¹¹C]1.